title: Oligoclonal bands and age at onset correlate with genetic risk score in multiple sclerosis.
abstract: BACKGROUND
  Many genetic risk variants are now well established in multiple sclerosis (MS), but the impact on clinical phenotypes is unclear.
  
  
  OBJECTIVE
  To investigate the impact of established MS genetic risk variants on MS phenotypes, in well-characterized MS cohorts.
  
  
  METHODS
  Norwegian MS patients (n = 639) and healthy controls (n = 530) were successfully genotyped for 61 established MS-associated single nucleotide polymorphisms (SNPs). Data including and excluding Major Histocompatibility Complex (MHC) markers were summed to a MS Genetic Burden (MSGB) score. Study replication was performed in a cohort of white American MS patients (n = 1997) and controls (n = 708).
  
  
  RESULTS
  The total human leukocyte antigen (HLA) and the non-HLA MSGB scores were significantly higher in MS patients than in controls, in both cohorts (P << 10(-22)). MS patients, with and without cerebrospinal fluid (CSF) oligoclonal bands (OCBs), had a higher MSGB score than the controls; the OCB-positive patients had a slightly higher MSGB than the OCB-negative patients. An early age at symptom onset (AAO) also correlated with a higher MSGB score, in both cohorts.
  
  
  CONCLUSIONS
  The MSGB score was associated with specific clinical MS characteristics, such as OCBs and AAO. This study underlines the need for well-characterized, large cohorts of MS patients, and the usefulness of summarizing multiple genetic risk factors of modest effect size in genotype-phenotype analyses.
authors.affiliation: Department of Neurology, Oslo University Hospital, Norway.
authors.forename: Hanne F
authors.initials: HF
authors.lastname: Harbo
authors.forename: Noriko
authors.initials: N
authors.lastname: Isobe
authors.forename: Pål
authors.initials: P
authors.lastname: Berg-Hansen
authors.forename: Steffan D
authors.initials: SD
authors.lastname: Bos
authors.forename: Stacy J
authors.initials: SJ
authors.lastname: Caillier
authors.forename: Marte W
authors.initials: MW
authors.lastname: Gustavsen
authors.forename: Inger-Lise
authors.initials: IL
authors.lastname: Mero
authors.forename: Elisabeth Gulowsen
authors.initials: EG
authors.lastname: Celius
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hauser
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Oksenberg
authors.forename: Pierre-Antoine
authors.initials: PA
authors.lastname: Gourraud
mesh_terms: D000328:Adult; D017668:Age of Onset; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D007074:Immunoglobulin G / Q000134:cerebrospinal fluid; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D043025:Oligoclonal Bands / Q000134:cerebrospinal fluid*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D007074:Immunoglobulin G; D043025:Oligoclonal Bands
keywords: Age of onset; Multiple Sclerosis Genetic Burden; cerebrospinal fluid; genetic association; genetic risk; genotype; multiple sclerosis; oligoclonal bands